Fibronectin Matrix Remodeling in Chronic Diseases

Immunofluorescence image of a fibronectin matrix formed by cells in culture

Fibronectin matrix polymerization in tissues is normally tightly-regulated. This ensures that fibronectin remains soluble in the plasma and is converted into insoluble, biologically-active fibrils only at appropriate sites. Inappropriate fibronectin matrix deposition occurs in several pathological conditions associated with tissue remodeling, including atherosclerosis, hypertrophic scar formation, pulmonary and renal fibrosis, and asthma.

Wound scrape assay showing enhancement of cell migration in response to fibronectin

In contrast, reduced fibronectin matrix deposition is associated with abnormal wound repair. We are currently asking questions about how chronic conditions such as diabetes and emphysema affect ECM remodeling and fibronectin function in tissues. Our questions include: How does chronic exposure to cigarette smoke affect extracellular matrix remodeling in the lung? Is fibronectin matrix assembly essential for normal wound repair and is this process dysregulated in chronic diabetic wounds? Can we develop methods to promote normal matrix assembly in damaged tissues?